This multicenter, randomized controlled trial aims to evaluate whether early initiation of supplemental parenteral nutrition (SPN) (on day 4 of ICU admission) compared to late initiation (on day 8) can reduce 28-day all-cause mortality in critically ill patients. Secondary objectives include assessing the effects of early SPN on long-term functional outcomes (2-year EQ-5D-5L scores), mortality at various timepoints (ICU, 28-day, 90-day, 180-day, and 2-year), ICU length of stay, serum prealbumin levels (days 8 and 28), skeletal muscle measurements (diaphragm thickness, biceps, quadriceps, and rectus femoris cross-sectional area), incidence of ICU-acquired infections, adverse events (e.g., hyperglycemia, hypoglycemia, dyslipidemia, liver dysfunction), and ventilator-free days within 28 days.
Eligible patients are adults (≥18 years) with at least one organ failure (SOFA score ≥2) within 24 hours of ICU admission, expected to remain in the ICU for \>72 hours, and unable to reach 50% of caloric target via enteral nutrition (EN) within the first 72 hours. A total of 946 patients will be enrolled and randomized to receive either early SPN (day 4) or late SPN (day 8) in addition to standard EN. Follow-up will include in-hospital assessments and telephone follow-ups at 28, 90, 180 days, and 2 years. The study hypothesizes that early SPN may improve short-term survival and nutritional/muscle status, though its impact on long-term quality of life remains to be determined.
Age ≥ 18 years
Failure of one or more organ systems within 24 hours of ICU admission, defined as Sequential Organ Failure Assessment (SOFA) score ≥ 2 in any single organ system
Expected ICU stay > 72 hours
Able to initiate early enteral nutrition (EN) within 48 hours of ICU admission
None
Parallel
Early Supplemental Parenteral Nutrition (SPN)
Dietary supplementSPN is initiated on ICU day 4 if enteral nutrition remains \<50% of the target caloric requirement. Nutrition support is guided by protocol
Late Supplemental Parenteral Nutrition (SPN)
Dietary supplementSPN is initiated on ICU day 8 if enteral nutrition remains \<50% of the target caloric requirement. Nutrition support is guided by the same protocol as in the early SPN group.
28-Day All-Cause Mortality
Death from any cause occurring within 28 days of ICU admission. This is a binary outcome (alive or dead). Lower mortality indicates better outcome.
physical function score： EuroQol 5-Dimension 5-Level Questionnaire（EQ5D5L）
The EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L) is a standardized instrument for measuring health-related quality of life. It includes five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each rated on five levels, and a visual analog scale (EQ-VAS) ranging from 0 to 100. The utility index score, calculated using the country-specific value set (e.g., China), typically ranges from \<0 (worse than death) to 1 (perfect health). Higher scores indicate better health status.
ICU Length of Stay
The number of days the patient remains in the intensive care unit (ICU), counted from the date of ICU admission to the date of ICU discharge. A higher number indicates longer ICU stay.
Serum Prealbumin Levels on Day 8, Day 28, Day 90, Day 180, and 2 Years
Serum prealbumin (transthyretin) concentrations will be measured at five time points (ICU day 8, day 28, and at 90 days, 180 days, and 2 years post-ICU admission). Venous blood samples will be used for laboratory analysis. Results will be reported in mg/dL. Higher levels indicate better nutritional status and recovery.
Muscle Ultrasound Measurements on Day 8, Day 28, Day 90, Day 180, and 2 Years
Muscle mass will be assessed by bedside ultrasound at five time points: ICU day 8, day 28, and at 90 days, 180 days, and 2 years post-ICU admission. Parameters include diaphragm thickness, biceps thickness, quadriceps thickness, and rectus femoris cross-sectional area. Ultrasound measurements will follow standardized anatomical landmarks and positioning. Higher values reflect greater muscle mass and better nutritional status.
Gastrointestinal Tolerance and Intestinal Function Indicators
Gastrointestinal symptoms (including vomiting, abdominal distension, diarrhea, and gastric retention) will be recorded daily. Nutritional status will be assessed using a standardized nutritional scoring tool (e.g., NRS-2002 or mNUTRIC). Intestinal dysfunction will be graded according to validated ICU scoring criteria (e.g., ESICM WGAP guidelines and GIDS socre). These indicators reflect enteral tolerance and gut function during nutrition therapy.
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Dong Zhang
Lead sponsor
The First Hospital of Jilin University
Sponsor institution
